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Facebook/PoliceMelissa Smith is accused of murder in the fatal shooting of her husband, Red Bank Police Officer James "Chip" Smith, in Tennessee.

Melissa Smith is a 37-year-old Tennessee woman who has been charged with first-degree murder after police say she shot and killed her husband, Red Bank Police Officer James Smith, during an argument in a parking lot in the Kodak community of Sevierville, Tennessee. James Smith, 41, who went by Chip Smith, was shot in the abdomen about 7:20 p.m. on Saturday, February 2, 2020, and later died at a nearby hospital, the Sevierville Police Department said.

The Red Bank Police Department said in a statement, Our thoughts and prayers go out to Officer Smiths family during this difficult time. Officer Smith has many years of law enforcement service. He honorably and faithfully served this agency and community. We want to take this opportunity to ask for everyones support during this very difficult time. Please keep his family, friends and fellow law enforcement family in your thoughts and prayers.

The Sevierville Police Department said officers responded to a shooting at 3099 Winfield Dunn Parkway, a highway rest stop and visitors center, at 7:23 p.m. on Saturday. The officers found an adult male suffering from a gunshot wound to the abdomen. He was taken to University of Tennessee Medical Center by the Sevier County Ambulance Service and was pronounced dead, police said. Police said a handgun was recovered at the scene and Melissa Smith was taken into custody.

Heres what you need to know about Melissa Smith and the fatal shooting of Red Bank Police Officer James Chip Smith:

Melissa Smith and James Smith.

Melissa Smith told police she was with her husband at the Old Tennessee Distillery Company for about two hours before the argument and shooting occurred and they had been drinking, according to court documents obtained by the Chattanooga Times Free Press. The newspaper reports that officers found Melissa Smith kneeling next to her husband with her hand on his abdomen after the shooting.

Melissa Smith told police she and her husband began arguing in the car after they left the distillery, and James Smith pulled into a parking lot as it escalated, the Times Free Press reported.

The two exited the vehicle and continued to argue until Melissa Smith went back to the vehicle, grabbed a pistol and shot James Smith, the newspaper wrote, citing court documents. Melissa Smith admitted to shooting James Smith with the pistol, according to court records. A .380 semi-automatic pistol was found at the scene.

Melissa Smith and James Chip Smith had been married since August 17, 2002, according to Melissas Facebook page.

The couple has a 14-year-old son together, according to Melissa Smiths Facebook page. They live in Soddy-Daisy.

FacebookMelissa and James Smith.

Chip Smith was arrested on domestic violence charges in 2007 while he was a detective with the Soddy-Daisy Police Department, according to an article in The Chattanoogan from the time.

According to a complaint obtained by The Chattanoogan, James Smith and his wife got into an argument that led to a physical confrontation. Police said Melissa Smith confronted her husband on a marital issue and he grabbed her and threw her across a bed onto their child, the news site reported.

Mrs. Smith said her husband was on top of her and began strangling her with his hands around her neck. She said they began screaming and hitting each other, the news site wrote. Mrs. Smith said she ran into another room and called 911 on her cell phone. She said her husband grabbed the phone from her and hung it up. She said he pushed her down on a couch, but she was able to get away. Officers said they saw injuries to the right side of Mrs. Smiths neck as well as injuries on her left arm.

The case was dismissed in January 2008.

Melissa Marlow Smith works at CHI Memorial Integrative Medicine Associates, a family medical practice in Chattanooga, according to her Facebook profile. It is not clear what her job at the medical practice is.

According to her Facebook page, she was born and raised in Soddy-Daisy, Tennessee, and graduated from Soddy-Daisy High School in 2000, two years before she and Chip Smith married.

Chip Smith is also from Soddy-Daisy, Tennessee, and graduated from Chattanooga State Community College, according to his Facebook page.

The Red Bank Police Department said in a statement posted to Facebook about the death of James Smith that they, lost an outstanding officer and friend yesterday.

James Chip Smith and his son.

The department said, He also served several other law enforcement agencies and communities including the Soddy-Daisy Police Department and Chattanooga Police Department. As a law enforcement officer, he devoted himself to protecting the citizens of these communities. For those that ever met him or know him, they know that he was kind and always willing to do anything to help you. His loss will leave a void at our agency and the law enforcement community.

Chattanooga Police told the Times Free Press, they are ready to provide any patrol or special coverage needed by Red Bank Police Department as they grieve the loss of their officer and friend.

The Hamilton County Sheriffs Office said in a statement, We are saddened by the loss of a fellow officer in such tragic circumstances. Our hearts go out to Chief Seymour and our brothers in blue at the Red Bank Police Department during this very difficult time. Chip has served his community for many years as both a volunteer fireman and law enforcement officer. He will be greatly missed by all who knew him.

On Facebook, the Hamilton County Emergency Medical Service wrote, Chip was both an on duty and off duty friend to many of us here at HCEMS, and we are devastated by the news of his death. Chip was also a well known individual in the Soddy Daisy community, and he will be mourned by many. Godspeed Brother.

Melissa Smith is being held at the Sevier County Jail, according to police. Smith was booked into the jail at 1 a.m. on February 2. She was charged with first-degree murder and carrying a weapon while under the influence, according to online jail records.

She is being held in $1 million bail and has a March 2 court date scheduled on the weapon charge and a March 20 court date on the murder charge. It is not clear if she has appeared before a judge already.

Smith could not be reached for comment by Heavy and it is not known if she has hired an attorney who could speak on her behalf.

The Sevierville Police Department said in a statement, The investigation is ongoing and no additional information is available at this time.

READ NEXT: Recent College Grad Shot Dead While Driving with Boyfriend

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Melissa Smith: 5 Fast Facts You Need to Know - Heavy.com

Its known that drinking more water can help lower the likelihood of urinary tract infections (UTIs) by flushing out bacteria present in the urinary tract. But what about the food we consume? Can what we eat (or avoid) help reduce the risk of a UTI?

The answer is yes, according to new research, published January 30 in Scientific Reports, which found that the overall risk of developing a UTI was lower in vegetarians compared with meat eaters.

RELATED: Is There a UTI-Causing Superbug Lurking in Your Gut?

The study took place in Taiwan, where investigators recruited participants from among volunteers of Tzu Chi, an organization of Buddhists who participate in a variety of charity and disaster-relief efforts. About one-third of the members are vegetarians, and all volunteers must agree to swear off alcohol and smoking to join the group.

Participants completed a food frequency questionnaire, which included whether they identified as a vegetarian. Individuals who said they were vegetarian but reported eating meat or fish as part of their diet were classified as non-vegetarians. After researchers excluded people under 20, those with incomplete questionnaires, and those with a history of UTI, 9,724 subjects remained: 3,257 vegetarians and 6,467 non-vegetarians.

Investigators followed participants from 2005 to 2014 through the National Health Insurance Program, which covers nearly 100 percent of the population, to identify any diagnosis of a UTI. At the end of the study period, 217 people in the vegetarian group had been diagnosed with a UTI compared with 444 people in the non-vegetarian group.

RELATED: What Is a Flexitarian Diet? What to Eat and How to Follow the Plan

That difference translated into a 16 percent lower overall risk of UTI for vegetarians compared with non-vegetarians. In a further subgroup analysis, a vegetarian diet was significantly associated with a reduced risk of UTI mainly in females, according to the authors.

After adjusting for various chronic conditions like hypertension, diabetes, and high cholesterol, the vegetarian diet seemed to have a protective effect against UTIs for women, but no distinct difference was found in males, the authors write. The risk reduction was also present in nonsmokers for uncomplicated UTIs which are those that crop up in otherwise healthy people.

Women are more likely than men to get a UTI; 60 percent of women will have at least one UTI in their lifetime compared with only 12 percent of men. This is because women have shorter urethras than men, meaning that bacteria has a shorter distance to travel to get to the bladder, according to the Urology Care Foundation.

Because vegetarian diets are associated with different bacteria flora in the gastrointestinal system, it isnt surprising that the risk of UTI was lower in this group, says Chin-Lon Lin, MD, the lead author and a professor at Tzu Chi University in Taiwan.

Dr. Lin suspects that the risk reduction is due to the combination of more vegetables and the elimination of meat. But we do think meat plays a more important role because it changes the intestinal flora, says Lin.

The strains of E. coli that cause the majority of UTIs are known as extraintestinal pathogenic Escherichia coli (ExPEC), and they can colonize and infect normally sterile body sites. Researchers theorize that by eliminating meat, particularly pork and poultry, which are known to contain these strains of E. coli bacteria, people are less likely to introduce the bacteria into their bowel and therefore lower the risk that the bacteria will travel to the urethra.

Another potential contributor could be the high fiber content in vegetarian diets. Because of the way fiber is metabolized, it decreases the pH in the gut, which in turn may inhibit the growth of E. coli, the authors write.

RELATED: 9 Things You Should Know Before You Go Vegetarian

Although these findings are intriguing, there are a number of other factors in the Buddhist lifestyle beyond dietary ones, says Yufang Lin, MD, an integrative internal medicine doctor at Cleveland Clinic in Ohio, who was not involved in this research. This makes it difficult to attribute the reductions in urinary tract infections to the effects of diet alone, she says. While I dont think this study provides conclusive evidence that a vegetarian diet reduces UTI risk, there are a number of things about the vegetarian diet that can support the reduction of UTI, says Dr. Lin.

The study authors acknowledge their findings have a few key limitations. They based the presence (or absence) of a UTI on the coding of the healthcare provider (ICD-9) rather than the gold standard, which would have been clinical symptoms and lab tests, including a urine culture. Factors that are known to influence UTIs, such as water intake and sexual activity, were not measured or accounted for in the findings.

According to Dr. Chin-Lon Lin, further research should include more analysis of the strains of bacteria that are responsible for UTI, which will shed light on the mechanism of the apparent protective effect of vegetarian diets.

In addition to reducing exposure to E. coli by eliminating meat, there are ways that eating more vegetables can reduce the risk of UTI, according to Dr. Yufang Lin. Many plant-based foods, particularly herbs or bitter foods, have antimicrobial properties and are also antioxidants, she says.

A vegetarian diet is often rich in components that are antimicrobial, says Lin. Antimicrobial means it has the ability to fight the presence of microbes, including bacteria. These work to suppress bacterial growth in the food that we eat as well as suppress bacterial growth in the gut, she says.

This is combination reduces the amount of bacteria in our intestinal environment, which in turn reduces the possibility of bacteria going to our bladder, she explains. This is how a vegetarian diet that has a lot of antimicrobials can be very beneficial, says Lin.

As part of the vegetarian diet youre also going to get a lot of foods that are antioxidants, says Lin. They are also supportive of our own immune system and as a result can also promote our ability to fight off infection, she says.

Finally, fruits and vegetables are rich in nutrients, which help support the bodys functions in general, says Lin. There are a lot of factors that support having a plant-based diet. You dont necessarily have to be a vegan for better health, she adds.

I absolutely think when you eat lots of whole foods, vegetables, fresh fruits, things of that nature, youre going to get multiple benefits and the potential to reduce UTIs, Lin says. For someone whose immune system is a little bit weaker, she recommends cooking with lots of spices such as garlic, onion, rosemary, thyme, oregano, ginger, all of which are antimicrobials and antioxidants, she says.

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Urinary Track Infection (UTI) Risk Reduced With Vegetarian Diet - Everyday Health

I want to make it clear right at the outset that I have a real aversion to injectables. Each to their own, really, and one must never say never. But today, when I say needles, Im not talking about Botox or fillers but acupuncture cosmetic acupuncture to be precise.

I started this treatment in January last year to prevent my endometriosis from recurring. My gynaecologist is a big believer in this 2,000-year-old science, and encouraged me to try the alternative route. The thing with acupuncture is that youll see changes in four to five sittings. Pain reduction, in fact, is instant. The degree of pain may be lesser in the first sitting, but soon youll find complete relief. I can say this with confidence because Ive experienced it.

In spring, as I began to feel better, I decided to try cosmetic acupuncture. Someone told me about a Delhi designer whose chronic acne got cured under the deft hands of Dr Adil Khan, my acupuncturist in Nizamuddin West, Delhi. He began practicing as a teenager with the senior Dr Khan, his father, and the man who first brought this practice to India. It made sense really, to work on my skin. I was going three times a week in any case needles on my body and my face was an optimum usage of time. I told Dr Khan to work on tightening my skin, especially the jawline. I could work on texture with skincare and radiance with food, but skin tightening has never been possible without daily massages, injectables or petit surgery.

I got several other women at the yoga studio to try cosmetic acupuncture with me. My friend who works in fashion went to de-puff her under-eye bags. In a few sessions, they were gone. My mother, too, is visiting the kind doctor for puffiness and cervical, and yes, its working for both. After the second sitting, my mothers face looks healthier and clearer, and she didnt feel dizzy when she made kheer in the evening. My mother calls acupuncture addictive because of the results. My fellow yoga teacher nailed it when she said that with this treatment, you get the kind of glow when youre in love, but without being in love.

And what about me? Sculpted, tightened and glowing. My facial contours look more defined and lifted when I get my treatments done regularly. But it is no injectable. These are just needles releasing the lymph, detoxifying the skin, and balancing qi (energy or prana). One integrative medicine expert called facial acupuncture a Botox alternative. The only caveat is that you have to get it done weekly. And thats the thing with holistic therapies regularity is essential. The other way to keep the skin lifted and tightened is facial massage. (Please Google Tanaka Face Massage and thank me later). But that should be done every day.

The point is that this is an easy, inexpensive treatment. There is nothing injected into the skin. The results are instant: you can (and must) get facial acupuncture before a party. What I find best about this technique is that theres a clear mind-body benefit. It is impossible to imagine drifting off to sleep with needles on your face and body, but it happens very naturally. Acupuncture trance is real: as the needles work on your internal and external health, youll find yourself falling into a light, lucid sleep. There are so many times when I go for a session after a night spent twisting and turning. When that happens I just ask Dr Khan to give me a few extra points for sleep, and I get my power nap for the day.

There are many centres in Delhi where you can get acupuncture like Dr Raman Kapur at Gangaram Hospital, who has helped many people with serious health problems. In Dehradun, theres Dr Jitendra Uniyal, and in Mumbai, Dr Jasmine Modi, who comes highly recommended by IVF specialist Dr Firuza Parikh. I travel from Gurugram to Nizamuddin (an hours drive) to get my needles. Im only sad that that I didnt discover it before.

A column to remind you about all things skin deep.

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Down to the needle: what to expect from cosmetic acupuncture - The Hindu

By Judith Smith-Meyer for Foodbank of Santa Barbara County | January 29, 2020 | 9:00 a.m.

The Foodbank of Santa Barbara County expands its public nutrition education series Food as Medicine with Digestion Connection: How Digestion Impacts States of Health and Disease, 6 p.m. Wednesday, Feb. 19, in Santa Barbara Public Library's Faulkner Gallery, 40 E. Anapamu St.

Admission is free, but seating is limited. To reserve seating, email [emailprotected] or call 805-357-5754.

Presented by local nutrition experts Vibeke Weiland and Randi Miller, the talk will cover the impact of digestive health on overall well-being and how to choose foods to improve digestion.

Participants will enjoy local wine and probiotic beverages, and will be able to taste freshly prepared recipes such as Italian wedding soup, mushroom soup, winter citrus salad, vegan stuffed mushrooms and fermented foods. Attendees will take home recipes for gut-friendly foods.

In conjunction with the talk, two new Food as Medicine free podcast episodes are available at https://foodbanksbc.org/get-help/fam.

Lacey Baldiviez, the Foodbanks nutritional biologist and director of community education, talks with Weiland and Miller about how the digestive process works, how to decipher clues from your body about the health of your digestive system, and ways to improve the health of your entire body by improving your gut microbiome.

The first new podcast episode, Digestion Connection, Part 1: Introduction to Digestion, explores the effect of digestive health on the rest of the body, including skin, sleep, neurological and autoimmune conditions; elimination and how it can affect hormonal balance.

Weiland and Miller discuss how to care for your gut microbiome, and how to eat for your best gut function. The podcast subtitle elaborates that, in this episode, listeners will learn why the gut is not Las Vegas, what normal digestion looks like in the toilet, and how to slow things down to get the most from your meals.

The second new episode, Digestion Connection, Part 2: Acid Reflux, Liver Detox and Gluten Specs, illuminates anatomy, digestive processes and strategies related to acid reflux/heartburn and G.E.R.D. (gastroesophageal reflux disease).

This podcast aims to teach about causes of acid reflux, how to eat to detoxify your body, and why you might consider testing glutens effects.

Weiland is a certified nutritional therapy practitioner practicing at Santa Barbara Wellness for Life in Santa Barbara, and is the immediate past chair of the Foodbanks board of trustees.

Miller is a certified health coach in integrative nutrition. She practices functional diagnostics nutrition, helping people optimize their health via diet and lifestyle based on lab test results and symptoms.

For more about the Foodbank of Santa Barbara County, visit http://www.foodbanksbc.org.

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Chew on This: Food as Medicine Series Examines The Digestion Connection - Noozhawk

When graphic designer Traci Klatkas anxiety began ratcheting up this summer, she knew she had to act.

The Pottsville woman, 40, was increasingly stressed by work and financial demands, including upkeep of the home she owns, but she didnt want to resort to medication.

So she added monthly reiki a traditional Asian energy healing practice to a self-care routine that already included regular exercise and massage.

The world we live in, its just stressful, said Klatka, who drives from Pottsville to Spring Township for services at the Salt Lounge. For me, stress starts as something emotional, and then it becomes physical as well.

Just as massage can relieve tension in tight muscles, it and other forms of stress relief can drive down the presence of key hormones that keep the brain in a heightened state.

Controlling stress may be especially important for women, according to an emerging body of research.

A study published in the journal Neurology in late 2018 found that people with higher cortisol levels had worse memory and visual perception, and they also had less gray matter in areas of their brains that control vision, memory and judgment.

The results were worst among middle-aged women.

And ladies, the bad news doesnt end there.

Older women who reported having stressful life experiences during their middle years were more likely to have greater memory decline later in life, according to a National Institute of Aging study published by Johns Hopkins researchers last summer.

The researchers said their findings add to evidence that stress hormones play an uneven gender role in brain health and align with already documented higher rates of Alzheimer's disease in women than men.

While the Johns Hopkins study looked at those who suffered traumatic events, it also asked participants about life experiences such as a marriage, divorce, death of a loved one, job loss, severe injury or sickness, a child moving out, retirement or birth of a child.

Munro said that that long-term stress, such as that experienced during a divorce, may more negatively impact brain function than short-term, traumatic events.

With so many mid-lifers stressed by daily demands including one in seven people trapped in the sandwich generation who are caring for both a child and an aging parent that could all be taken as bad news.

But theres no need to add more to your list of things to worry about.

"We can't get rid of stressors, but we might adjust the way we respond to stress, and have a real effect on brain function as we age," said Dr. Cynthia Munro, associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "And although our study did not show the same association for men, it sheds further light on the effects of stress response on the brain with potential application to both men and women.

Feel it

Though the long-term effects of stress may be different on men and women, everyone can feel it their mind and body.

Registered nurse Paula Martin opened a Massage Envy franchise in Wyomissing after coming to appreciate the way regular sessions helped her muscles recover from tough spinning, running or Cross Fit workouts. For many of her clients, a regular massage is also part of a stress-relief routine that calms the mind.

Though she sees just as many male as female clients maybe more women tend to complain about headache more often. Those may be exacerbated by stress.

Regardless of gender, tension is often stored in the same areas: shoulders, back and neck. But women, Martin said, may not visit for a workout as often and then have more to be worked out during a visit.

We spread ourselves too thin, said Martin, who offers memberships and recommends monthly visits. But Massage really does have a cumulative effect. Its something that you can practice on a more regular basis, much like meditation or yoga.

Massage releases endorphins that counter the anxiety-inducing effects of cortisol. For some customers, add-ons like aromatherapy oils or hot stones may up the calm factor. Soothing music, low lighting and warmth also prompt the body to relax.

Identifying things that help promote relaxation and making them part of a regular routine can help lower cortisol levels, reduce physical tension that can lead to injury or physical limitations and set individuals up for better long-term health.

Klatka continues to seek the right combination of tools. She cut back on some of her more high-intensity workouts, which research has found can trigger more cortisol to be released. Instead, she does yoga several times a week and walks on her treadmill or outside when weather allows.

Alleviated symptoms

Though she was skeptical about Reiki, she found the first visit alleviated symptoms such as a racing heartbeat and racing thoughts for more than three weeks.

From the moment I laid down on the table, I could feel the change in my body, Klatka said. You go into this relaxed state where youre not quite asleep but not quite awake. It just happens naturally for me.

Theres no magic bullet when it comes to managing stress.

Ampersand Integrative Wellness opened in Wyomissing in December. Practitioners there offer a variety of services personal training, nutrition counseling, massage and yoga that can all lead to stress relief.

Yoga and meditation instructor Ariana Miley said she sees differences in how men and women store tension in their bodies. Men often repress their stress and that manifests in tension in their bodies, limiting flexibility. Women, she said, may be more open to talking about their emotions but they still carry significant tension in their hip flexors.

Her Yin yoga class includes 3- to 5-minute poses that allow the hips and the rest of the body to relax and allow the mind an opportunity to follow.

A lot of times, with breathwork and meditation, that trauma, including everyday stress, can come to the surface, Miley said. Even if its 10 minutes a day or an hour a week, people who commit to a practice are more able to focus and concentrate on the task at hand.

At Salt Lounge, just down the road, owner Rachel Eskin has continued to broaden her wellness offerings. In 2020, she is focusing events and classes around guided meditation practices.

Klatka continues to drive nearly an hour to get to her appointments after finding a place where she is comfortable that provides a service that works for her.

If its a chronic condition for you and youre not sleeping, its going to affect your memory, your body, your organs, she said. Its worth the $50 or whatever, and its better than spending it at the doctors office.

Contact Kimberly Marselas: specialsections@readingeagle.com.

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Hormones play an uneven gender role in brain health; are linked to higher Alzheimer's disease in women than men - The Reporter

NEW YORK Last month, Cytovia Therapeutics unveiled two partnerships in succession: one with the New York Stem Cell Foundation, and one with Justin Eyquem's laboratory at the University of California, San Francisco. These partnerships, which contain a three-year research agreement between the three institutions, will support Cytovia's foray into developing natural killer (NK) cell-based therapies for cancer.

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Cytovia's CAR NK Alliance With NYSCF, UCSF Aims to Overcome Negative Side Effects of CAR T Drugs - Precision Oncology News

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Global Cell Proliferation Kit Market Growth, Size, Share and Rising Trends Analysis Research Report 2024 - NY Telecast 99

Ethnic and racial minority populations in the U.S. have a long history of being mistreated by the health care system, researchers and the government. The resulting mistrust can pose a challenge for researchers seeking to understand the biology of complex traits, as well as for physicians interested in delivering personalized care to diverse patients. Diversity in precision medicine research is crucial for understanding genetic differences that shape so many health outcomes and potential treatments.

Learn what physicians and health systems can do to advance precision medicine research and build rapport and trust to increase minority participation in critical research.

Genetics and precision medicine have become increasingly important in effective patient care. Through its partnerships and research, the AMA is advancing the ethical implementation of precision medicine.

About 10% of the worlds population is of European ancestry. However, this population accounts for 78% of genetic study participants. The National Institutes of Healths All of Us Research Program aims to address this disparity in medical research by enrolling 1 million or more participants to gather data on a wide variety of health conditions.

The AMA has partnered with the All of Us program, which aims to enable a new era of medicine through research, technology, and policies that empower patients, researchers and providers to work together to develop individualized care. This program is intended to gain better insights into the biological, environmental and behavioral influences on disease to enhance prevention and treatment.

The AMA Ed Hub module, All of Us Research Program: Informing the Future of Health Care, is enduring material and designated by the AMA for a maximum of 0.75 AMA PRA Category 1 Credit.

Learn more about AMA CME accreditation.

There are currently more than 320,000 All of Us participants, with about 250,000 having completed the initial steps of the program. Nationwide, more than 50% of All of Us participants are members of racial or ethnic minority groups. And in Illinois, more than 80% are from groups that have traditionally been underrepresented in biomedical research.

Joyce Ho, PhD, is a research assistant professor and lead investigator for the All of Us Research Program at Northwestern University Feinberg School of Medicine in Chicago. Ho shared how she and her colleagues in Illinois are engaging a diverse pool of participants, and offered advice for how physicians can help.

Were on track to build a sample of 1 million or more participants in the next five years or so, said Ho, adding that Illinois has more than 26,000 participants in the All of Us program to date. The Illinois Precision Medicine Consortium, which includes the University of Illinois, University of Chicago, Rush University Medical Center, NorthShore University Health System, and Cook County Health, is also in the lead nationally for how diverse their participant pool is.

The effort thats needed to reach diverse populations is something that we were prepared to put in, she said. We understood just from the history of research in this countryespecially with underrepresented populationsthat its not just, Hey, heres a consent form, please read it and we know you will participate.

Instead, trust must be built through providing honest and accurate answers to patients questions about precision medicine, the privacy and security of patients data, and more.

Those are all concepts that, regardless of how much you know about biomedical research, or whether you have participated in studies, you deserve a thorough explanation, said Ho.

Learn how to answer patients top five questions about the All of Us Research Program.

The actions of past medical researchers have earned much distrust in minority communities, making it crucial to treat these diverse populations as partners.

Nationally, even at the beginning of designing the All of Us Research Programbecause we know that we have this goal of building a diverse research databasewe made sure that participants are our partners, said Ho.

Participants from all walks of life should be included and valued in the design of the program. Everyone plays a major role.

The National Institutes of Health and its All of Us Research Program partners conducted focus groups to look at everything from participating in research to concepts about precision medicine and sharing data, said Ho. Theres a lot of work ... that we put in to understand how we can really build this resource in a way that includes what different communities want so that we really can benefit the health of people who are living in this country.

One of the most important ways that All of Us Research Program researchers in Illinois have approached this program is in the collaboration of community organizations, health systems and participants. All of Us Research Program investigators in Illinois have decades of experience working with diverse communities in biomedical research.

Transportation is often a barrier to working with underrepresented communities. It can prevent patients from receiving the health care they need. In Illinois, though, mobile clinical research units have allowed researchers to better reach these communities.

Researchers drive these research vehicles containing exam rooms to different communities to engage people about the program. They also leverage long-standing relationships with area churches, community organizations and clinics to engage community members.

That breaks down a lot of the barriers with transportation that happens in many of the communities here in Chicago, said Ho. It really makes a big difference in terms of being able to reach this community.

Engagement is keyin creating a diverse community of participants for precision medicine and biomedical research.

When we go out to talk to folks, we dont immediately ask people to participate. A lot of times, we just have great conversations with people about biomedical research, said Ho. A lot of times we are addressing a potential mistrust that has very reasonably existed in different communities.

For example, the University of Chicago has developed curriculum aimed at addressing mistrust, biomedical research and importance of research inclusion, especially among the African American community.

Our teams develop different engagement tools and strategies to reach communities that have been underrepresented in research, she said, adding that it goes beyond talking to someone for five or 10 minutes before they participate.

Instead, it is multiple conversations over time, and letting participants know that we aim to return health information back to them and perhaps in the future, they might decide to participate, said Ho.

And once participants have shared their information, it is important to reiterate that there will be a waiting period.

One of the challenges is to really explain to participants this is a long-term program and it really takes a lot of time and patience for us to be able to return the value back to you that you deserve, she said.

One of the missions of the program is not just building 1 million people and collecting all this data. Its just to have substantive conversations with people about the importance of inclusion in biomedical research to build awareness, she said.

By creating awareness around precision medicine and building trust within these communities, it is paving the way for future conversations.

Even if theyre being approached by another research group, theyll have a little more trust and understanding about why participation and representation is so important, said Ho.

Illinois All of Us researchers also have a community participant advisory board that provides feedback on the program. Together they discuss additional ways to engage Illinois communities.

These meetings cover items such as how to provide clinically relevant information to participants, which is one of the hallmarks of the program, Ho said. Were not just grabbing the data. Were also planning to return information back to participants.

Not only does the program have a 1-million-person database to build, but they need to have an infrastructure that is ready to process the volume of data and biosamples, while also prioritizing data security and privacy.

Our program spends a lot of resources building as secure of a data system as possible, said Ho, adding that there is also a whole pipeline of generating genomic data and clinically relevant data to return to participants.

Many people are wondering about the security and privacy of the data, so we need to not just build a very secure system, but be able to explain to people what the risks might be so that people can make an informed decision, she said.

One way that the All of Us program is building a robust research resource, is to include EHR data from participants. However, it is important for participants and physicians to know that the data is securely sharedall personal identifiable information is removed.

Data collected will be connected to other data types such as self-reported information, which includes health background and behaviors, as well as medical history, physical measurements and data gleaned from biosamples.

Theres a wide variety of longitudinal data were collecting from participants. Through a research data portal that the program is building, researchers will eventually be able to access data and samples to accelerate medical discoveries for diverse populations. Thats powerful, said Ho.

View post:
7 ways to expand diversity in precision medicine research - American Medical Association

Researchers at Harvard Medical School and Boston Children's Hospital have found a potential treatment for hereditary deafness, the same condition thought to have caused Ludwig van Beethoven to lose his hearing.

The scientists are using a new gene-editing approach that they say could someday prevent profound hearing loss.

Beethoven's Symphony No. 5 is a cornerstone of classical music. It is hard to believe the composer was almost completely deaf from a genetic condition when he finished it.

"These children are born fairly normal, but then over 10 or 20 years, they lose their hearing," Harvard neurobiology professor Dr. David Corey.

Aptly named "Beethoven mice" might hold the key to a potential cure. Scientists believe the animals have a defect in the same gene that may have caused Beethoven's deafness.

"Our genome is composed of about 3 billion letters of DNA that together make up 20,000 genes," Corey explained. "For the disease we're studying, one mistake in the DNA in one of the genes causes deafness."

Researchers identified that hearing gene called TMC1. It's a gene that comes in pairs.

Using a newly refined gene-editing system, they disabled the defective copy of the TMC1 gene, leaving the good gene in place.

"By eliminating just the bad copy, that would be sufficient to preserve hearing," Corey said.

The scientists then delivered the edited DNA back into the cells of the mice and tested their hearing.

"We put little scalp electrodes on the back of the head, play sounds into the ear and can measure the brain activity in response," Boston Children's Hospital professor of otolaryngology Dr. Jeffrey Holt said.

Researchers say the mice were able to hear sounds as low as 45 decibels, the level of a quiet conversation.

"This could be life-changing," Holt said.

A famed composer, his namesake mice and a team of scientists are using cutting-edge medicine to help people who would otherwise go deaf.

The scientists say this research paves the way for using the new editing system to treat as many as 3,500 other genetic diseases that are caused by one defective copy of a gene.

It's important to note that Holt holds patents on TMC1 gene therapy.

MEDICAL BREAKTHROUGHSRESEARCH SUMMARYTOPIC: BEETHOVEN MICE PREVENT DEAFNESS: MEDICINE'S NEXT BIG THING?REPORT: MB #4689

BACKGROUND: In the United States, hearing loss affects 48 million people and can occur at birth or develop at any age. One out of three people over the age 65 have some degree of hearing loss, and two out of three people over the age 75 have a hearing loss. Children in the United States are estimated at 3 million in having a hearing loss, and of those, 1.3 million are under the age of three. One of the leading causes of hearing loss is noise, and while preventable, can be permanent. Listening to a noisy subway for just 15 minutes a day over time can cause permanent damage to one's hearing. Listening to music on a smartphone at high volumes over time can cause permanent damage to one's hearing as well. The number of people with hearing loss is more than those living with Parkinson's, epilepsy, Alzheimer's, and diabetes combined. (Source: https://chchearing.org/facts-about-hearing-loss/ and https://hearinghealthfoundation.org/hearing-loss-tinnitus-statistics/)

TREATMENTS: The treatment you receive will depend on the cause and severity of the hearing loss. A reversible cause of hearing loss is earwax blockage where your doctor may remove earwax using suction or a small tool with a loop on the end. Some types of hearing loss can be treated with surgery, including abnormalities of the ear drum or bones of hearing (ossicles). Repeated infections with persistent fluid may result in your doctor inserting small tubes to help your ears drain. If your hearing loss is due to damage to your inner ear, a hearing aid can be helpful. With more severe hearing loss and limited benefit from conventional hearing aids, a cochlear implant may be an option. Unlike a hearing aid that amplifies sound and directs it into your ear canal, a cochlear implant bypasses damaged or nonworking parts of your inner ear and directly stimulates the hearing nerve. (Source: https://www.mayoclinic.org/diseases-conditions/hearing-loss/diagnosis-treatment/drc-20373077)

GENE EDITING WITH CRISPR: Scientists at Harvard Medical School and Boston Children's Hospital have used a newly tailored gene-editing approach in mice thought to have the same genetic defect that caused famed composer Beethoven to go deaf in adulthood. CRISPR-Cas9 gene editing works by using a molecule to identify the mutant DNA sequence. Once the system pinpoints the mutated DNA, the cutting enzyme, or Cas9, "snips" it; however, the gene editors are not always accurate. Sometimes, the guide RNA that leads the enzyme to the target site and the Cas9 enzyme are not precise and could cut the wrong DNA. The Harvard and Boston Children's scientists are using a modified Cas9 enzyme derived from Staphylococcus aureus bacteria that they are finding is significantly more accurate. (Source: https://hms.harvard.edu/news/saving-beethoven)

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'Beethoven mice' prevent deafness: Medicine's next big thing? - WNDU-TV

It is important to note that a pill to cure HIV is not simply around the corner, Dr. David Margolis, director of the UNC HIV Cure Center, said.

Some of the challenges of the virus include how it integrates itself into the genetic material of human cells, Chahroudi said.

"In a way, it becomes a foreign gene that is living in the human cell," Margolis said. "That cell looks like any other cell in the body, so there is no drug or immune response that can see it. Once the sleeping virus is re-awoken, it spreads."

The long-lived persistence of the HIV virus in the body makes it difficult to eradicate, due to latently infected cells that escape the bodys immune system, according to UNC's HIV Cure Center.

When it is silent and integrated into the host cell genome, it is not visible to the immune system, and so the immune system basically doesnt have a way to attack it when its in this latent form, Chahroudi said.

People who are infected with HIV and treated with standard antiviral treatment which is effective at suppressing virus replication are still at risk by HIVs nature, Chahroudi said.

In order to try to enable the immune system to now be able to see the virus in patients or monkeys or mice who are treated with AVT you need to test different approaches to try to reverse that latency, Chahroudi said. That basically means reawakening the virus, or activating the virus, in order to now express viral antigens that can be seen and targeting by the immune system.

The work on this project began in conjunction with the beginning of the UNC and ViiV Healthcare Limited partnership, said Richard Dunham, adjunct assistant professor in the UNC HIV Cure Center and director at ViiV Healthcare.

Its really born at the interface of industry, academia, here at Qura," Dunham said. "We started on this work back in 2016/2017 and then worked our way from the lab to the mouse to the monkey over the last several years.

Chahroudi said that despite the new research discoveries, no cure has been discovered.

Neither of them was able to reduce the level of what we call reservoirs, which is basically a persistent virus that's in cells, Chahroudi said.

Dunham said that about five years ago, UNC and ViiV Healthcare came to the realization that they could make more substantial progress toward curing HIV by working together. In the years that followed, the institutions created Qura Therapeutics and the UNC HIV Cure Center to conduct research.

Emory University's HIV research team was added to further the partnership.

The overall principle here is that no one entity is really going to make that progress against HIV," Dunham said. "We feel like this partnership between industry and academia might help us to take these different and diverse approaches between the two types of organizations to work together to find an HIV cure."

Chahroudi said the next steps for the research include combining both of the latency-reversing strategies discovered at UNC and Emory to boost the immune response against the affected cells.

If were able to reawaken or reactive the virus and then treat the animals with different immune-boosting or aiding strategies, we hope that combination may have an impact on the level of virus reservoirs, Chahroudi said.

The goal for researchers at UNC is to make the chemical that treats latent cells into a drug that can be used in people, Margolis said.

university@dailytarheel.com

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UNC researchers contribute to breakthrough in HIV cure research - The Daily Tar Heel

SAN DIEGO, January 31, 2020Human Longevity, Inc.(HLI),an innovator in providing data-driven health intelligence and precision health to physicians and patients, announced the publication of a ground-breaking study in the journalProceedings of the National Academy of Sciences(PNAS). The study titled, Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging, showed thatby integrating whole-genome sequencing with advanced imaging and blood metabolites, clinicians identified adults at risk for key health conditions.Data from 1190 self-referred individuals evaluated with HLIs multi-modal precision health platform, Health Nucleus, show clinically significant findings associated with age-related chronic conditions including cancer, heart disease, diabetes, chronic liver disease, and neurological disorders leading causes of pre-mature mortality in adults.

The goal of precision medicine is to provide a path to assist physicians in achieving disease prevention and implementing accurate treatment strategies, said C. Thomas Caskey, MD, FACP, FACMG, FRSC, chief medical officer for Human Longevity, Inc., lead author of the study, and a member of the National Academy of Sciences. Our study showed that by employing a holistic and data-driven health assessment for each individual, we are able to achieve early disease detection in adults.

Study highlights include:

This study shows that the definition of healthy may not be what we think it is and depends upon a comprehensive health evaluation, said J. Craig Venter, PhD, founder, Human Longevity, Inc. and a member of the National Academy of Sciences. The data underscore Human Longevitys innovative approach to helping clinicians with early detection and personalized treatments, potentially achieving better health outcomes for patients.

Our traditional approach to the annual health assessment has been very superficial and will need to be replaced by data-driven measures that will be made possible as costs continue to decline for whole- genome sequencing, advanced imaging, especially MRI, and specialized blood analytics, said David Karow, MD, PhD, president and chief innovation officer, Human Longevity, Inc.

ABOUT THE STUDY

The study cohort was composed of 1190 self-referred participants who enrolled at Health Nucleuswith a median age of 54 y (range 20 to 89+ y, 33.8% female, 70.6% European). A multidisciplinary team, including cardiologists, radiologists, primary care physicians, clinical geneticists, genetic counselors, and research scientists, integrated deep phenotype data with genome data for each study participant.Participants were enrolled in the study between September 2015 and March 2018.

ABOUT THE HEALTH NUCLEUS

Health Nucleus is Human Longevitys premier health intelligence platform utilizing state-of-the-art technology to provide an assessment of current and future risk for cardiac, oncologic, metabolic, and cognitive diseases and conditions. This is provided through a proprietary, multi-modal approach, integrating data from an individuals whole-genome sequencing, brain and body MRI imaging, cardiac CT calcium scan, metabolomics, advanced blood test, and more. The health assessment is conducted at Human Longevitys Health Nucleus precision medicine center in La Jolla, California.For more information, visitwww.healthnucleus.com.

ABOUT HUMAN LONGEVITY

Human Longevity, Inc. (HLI)is a genomics-based,health intelligence companyempowering proactive healthcare and enabling a life better lived. HLIs business focus includes the Health Nucleus, a genomic-powered, precision medicine center which uses whole-genome sequencing analysis, advanced imaging, and blood analytics, to deliver the most complete picture of individual health. For more information, visitwww.humanlongevity.com.

# # #

For more information, contact: Debbie Feinberg, VP of Marketing, Human Longevity, Inc., 858-864-1058,dfeinberg@humanlongevity.com

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Human Longevity's Largest Study of its Kind Shows Early Detection of Disease and Disease Risks in Adults - Cath Lab Digest

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Dr. Mahendran Mahadevan, a professor in the Department of Obstetrics and Gynecology at the University of Arkansas for Medical Sciences, willspeakfrom 3-4 p.m. Monday, Feb.3, in Room D2 of the Food Science Building, 2650 N. Young Ave. His presentation, "Food, Health, and Disease,"is open to everyone.

Mahadevan's presentation will focus on how different types of food and beverages plays a role in human body's health defense systems (Angiogenesis, stem cells/regeneration, microbiome, DNA protection, and immunity). This basic biological knowledge related to foods will be useful for better understanding about the effects of foods on the prevention and management of human diseases.

Mahadevan's research interests include: 1) roles of genetics, obesity, nutrition, food supplements, nutraceuticals, physical activity and other environmental/life style factors on prevention/public health and maternal, fetal, and child health; 2) tissue banking; 3) embryo and stem cell culture/expansion (particularly culture medium/conditions); and 4) gene therapy and stem cell gene therapy particularly in cancer and genetic diseases.

Mahadevan received his Veterinary medicine degree in 1975 from University of Ceylon Peradeniya, Sri Lanka and his doctoral degree in Reproductive biology from Monash University, Australia in 1982. His academic experience includes faculty positions in the Department of Physiology, School of medicine at the University of Ceylon and in the Department of Obstetrics and Gynecology at the University of Arkansas for Medical Sciences.

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UAMS Professor to Present Relationships Among Food, Health, and Disease in Food Science Seminar - University of Arkansas Newswire

Investment Thesis

Objective: Wealth-building of an always fully-invested portfolio via repeated near-term (weeks or months) capital gains from careful, diversified, odds-on issue selection and timely price opportunity capture.

The stocks compared here are Sarepta Therapeutics, Inc. (NASDAQ:SRPT) and Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR). SRPT was inadvertently omitted from the Biotech Developer review recently published. Rather than picture it by itself, ARWR is provided here as a best-ranked alternative.

These market pros have insights you and I can't have because their everyday job is to satisfy investment organizations running billion-dollar portfolios who want to adjust their holdings in multi-million-dollar trade transactions. These market-makers [MMs] have to round up sellers when their clients want to buy, and buyers when they want to sell. That's hard to do when most investors will hold off to get better prices, whether they are buying or selling.

And when lots of money is involved in each trade, the players get pretty careful about what they want to do and when they will do it. But the big-money types work hard to be on top of developments, following some issues intently, anticipating what is likely to be happening to stock prices in the near future. Depending on what they know, or think they know, and what they think others believe is likely to happen, they may take surprising postures. Often their holding-period horizons are months, not years. Or even less.

So, the MMs have to respond when a big-money house says "sell a bunch of this and buy a lot of that, and do it in the next 15 minutes, or you can forget about keeping us as a good repeat-order client".

The MMs will round up any of their other clients who they know have holdings in the stocks or appetites (at a price) to initiate, expand or contract holdings in the issues involved. It's rare when a "cross" can be made with enough "other side of the trade" exists at acceptable prices to "fill" the trade order without having to put some of their own firm's capital at risk in order to balance buying demand with selling supply.

As market-makers, they will provide the balancing position when they can set up a hedge deal to protect the market risk involved in their "facilitation" of the trade's being completed. If they can't, then the trade order gets killed, not filled, to wait for a time when the market is more accommodating.

But what it takes to buy that market risk price-change protection for the MM tells what the players on both sides of the "insurance" market believe can happen to the stock's price during the limited lives of the derivative contracts for options, futures, swaps, or other highly leveraged involved instruments used in the hedge.

That's where we find the balances between forecast upside price gain prospects and price drawdown exposures today and can compare them with what has been seen day by day over the past couple of decades. That is what supports the opening statements above about +15% to +30% gains in specific stocks. Those are fact-based histories of all prior real-market experiences from forecasts made before the fact, not just blown smoke over some after-the-fact single illustration of convenient history.

"Sarepta Therapeutics, Inc. focuses on the discovery and development of RNA-based therapeutics, gene therapy, and other genetic medicine approaches for the treatment of rare diseases. The company offers EXONDYS 51, a disease-modifying therapy for Duchenne muscular dystrophy (DMD). Its products pipeline include Golodirsen, a product candidate that binds to exon 53 of dystrophin pre-mRNA, which results in exclusion or skipping of exon during mRNA processing in patients with genetic mutations; and Casimersen, a product candidate that uses phosphorodiamidate morpholino oligomer [PMO] chemistry and exon-skipping technology to skip exon 45 of the DMD gene. In addition, the company's pipeline comprises SRP-5051, a peptide conjugated PMO that binds to exon 51 of dystrophin pre-mRNA. It has collaboration agreements with Nationwide Children's Hospital to advance micro-dystrophin gene therapy program under the research and license option agreement; Galgt2, a gene therapy program for the treatment of DMD; and Neutrophin 3, a gene therapy program to treat Charcot-Marie-Tooth neuropathies. The company also has a license agreement with Lysogene to develop LYS-SAF302, a gene therapy for mucopolysaccharidosis IIIA; a license and option agreement with Lacerta to develop treatments for CNS-targeted and lysosomal storage diseases; and research collaboration and option agreement with Genethon to develop micro-dystrophin gene therapy products. In addition, it has a research agreement with Duke University to advance gene editing CRISPR/Cas9 technology for restoring dystrophin expression; a collaboration agreement with Summit (Oxford) Ltd. to commercialize products in Summit's utrophin modulator pipeline; a strategic collaboration with Paragon Bioservices; and a strategic collaboration with CENTOGENE for the identification of patients with DMD in the Middle East and North Africa region. Sarepta Therapeutics, Inc. was founded in 1980 and is headquartered in Cambridge, Massachusetts."

Source: Yahoo Finance

SRPT's and ARWR's recent daily price ranges over the past 6 months are shown in Figures 1 and 2, along with measures of their current forecast price up-to-down balances. Also shown are the odds of long position gains being earned in the couple of months subsequent to points in time in the past 5 years when MMs had the same kind of outlook they have today.

Figure 1

source: Author

Figure 2

source: Author

As a contrast, here is what MM forecasts for the "market-index" ETF of SPDR S&P 500 Trust (SPY) looks like at this time:

Figure 3

source: Author

How effective the MMs have been in forecasting for these stocks is a matter of market records, when conditions of uncertainty similar to today's are examined. That was done in the row of data between the graphics of Figures 1-3. For ease of comparison, they are repeated and slightly expanded in Figure 4.

Figure 4

source: Author

As explained in the prior Biotech Developer revue featuring ARWR, the SRPT Range Index [RI] of 23 produced 108 of 124 net gain %Payoffs under TERMD of +30.1%.

A comparison of the +30.1% payoffs with the present forecast of +23.1% suggests an exceptional profit achievement with a degree of credibility for the current outlook of 1.30, as indicated at column [N] of Figure 4.

So much for the "good side" of a buy proposition; what about the "bad side"?

As we condition the credibility of the upside price change forecast by comparison with actual experience, so too do we look to see how bad the downside might get. But with concern only during those "long" holding periods when committed capital would be at risk under the TERMD discipline. All other periods are irrelevant, shocking as they may be.

Figure 1's data row tells what the worst case price drawdowns have been (an average of them) during all of each actual exposure period when they were to be held. What matters is how bad a fear of loss may get induced any time, not just whether or not it existed at the end of the holding. Investors will have varied reactions to the exposures, so there is no way to evaluate potential risk impact by historic outcomes. But some useful guidance may be provided by having knowledge of the maximum degree of intensity possibly becoming present.

One logically-simplified way to address the combination of stock price risk and reward is to weight each part by its probability and combine the two. The "Win Odds" of profitable position odds here for SRPT of 108 out of 124, or 87 out of 100 offer such a probability. One minus those odds, or 100 - 87 provides the loss probability weight. Thus 0.87 times +30.1% plus 0.13 times -8.7% produces a weighted net payoff of +25.1%.

To make this style of evaluation more comparable between varied investment opportunity situations, an integration of the likely holding periods used in the calculation is helpful. For SRPT, the average number of market days required by all 129 positions of the sample was only 40 out of the maximum 63 possible, because of the high proportion of upside target prices reached.

A standard evaluation measure used in many capital planning decision situations is the expected net payoff stated in "basis points" of 1/100ths 1%, per day of capital involvement. On a 365-day calendar year +19 bp/day when sustained for a year doubles the original capital, or a CAGR of +100%. When a smaller-count of 252 market days makes up a relevant year, the fewer days are each proportionally more powerful, so only 14 bp/mkt day does the 100% equivalent.

Comparison is the essence of evaluation. If the investing objective is to make capital as productive of future spend-able amounts as possible, using an odds-weighted bp/d yardstick can be helpful.

To that end, Figure 4 includes the relevant MM forecasts and their prior outcomes for ARWR and the market-index proxy of the SPDR S&P 500 Index ETF (SPY). Also, the average of some 2,700 current-day MM price-range forecast issues, and a ranked set of the day's likely 20 best of those near-term wealth-building stocks under TERMD portfolio discipline.

All of these comparisons in Figure 4 have the same basic data as included in the row of Figure 1 for SRPT. That is expanded by the columns [O] through [R] to provide for odds-weighted bp/day price-prospect evaluation comparisons.

Competition from the market-index alternative SPY at this point in time is rather limited because of an unenthusiastic upside target outlook of only +5.5% at a CAGR of only +9% and an Odds-Weighted net prospect [Q] of +0.8%. That is better, though, than the overall population of 2,711 where MM forecasts are a modest net decline (-2.2%).

Sarepta Therapeutics, Inc. and Arrowhead Pharmaceuticals Inc. both offer outstanding prospects for capital gains with strong odds for achievement in short periods of holding. SRPT has the larger potentials, but ARWR appears historically to have quicker achievement prospects. Payoff potentials in basis points per day are exceptional. For further information, please check my blog here on Seeking Alpha.

Disclosure: I/we have no positions in any stocks mentioned, but may initiate a long position in SRPT over the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: Disclaimer: Peter Way and generations of the Way Family are long-term providers of perspective information, earlier helping professional investors and now individual investors, discriminate between wealth-building opportunities in individual stocks and ETFs. We do not manage money for others outside of the family but do provide pro bono consulting for a limited number of not-for-profit organizations.We firmly believe investors need to maintain skin in their game by actively initiating commitment choices of capital and time investments in their personal portfolios. So, our information presents for D-I-Y investor guidance what the arguably best-informed professional investors are thinking. Their insights, revealed through their own self-protective hedging actions, tell what they believe is most likely to happen to the prices of specific issues in coming weeks and months. Evidences of how such prior forecasts have worked out are routinely provided in the SA blog of my name.

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Sarepta Therapeutics, Inc. And Arrowhead Pharmaceuticals Now Top-Ranked Biotech Stock Buys - Seeking Alpha

With the NFL Championship game this Sunday, all eyes turn to Whitehouse native and Kansas City Chiefs quarterback Patrick Mahomes.

Over the course of the last couple weeks, CBS19 has spoken to everyone from Mahomes father, Pat Mahomes Senior, his trainer at APEC, Bobby Stroupe, and fans across the region. Mahomes environment clearly helped forge him into a future NFL MVP.

Dr. Ushimbra Buford, a psychiatrist at UT Health Science Center at Tyler says there are crucial mental aspects of becoming an elite athlete.

Buford says the phrase nature vs nurture which references conflicting theories on whether the natural instincts with which people are born or the environment in which they are brought up has more of an impact on their development, is now somewhat outdated.

When I first started in medicine, we used to say things like nature and nurture and saw them as two different things. In the past several years with the advent and understanding of epigenetics, we understand now that the nurture aspect influences the nature, the environment influences your genetics, Buford said.

Buford says a persons development in all aspects, including athleticism, is heavily influenced by their environment, down to changes their body makes at a biological level.

From a genetic standpoint, that person may have a certain kind of capacity for the muscle fibers that they will produce that they were born with. But then they get into an environment where the expectation and the understanding and like the daily living is different from what their body is genetically set. Over time, their composition would change to reflect the activities they were involved in, and the potential reality exists that over time their genetics would change to reflect the new physical reality, Buford said.

This means growing up in an environment, such as in Mahomes case, where his father is a professional baseball player and he was immediately around athletics, can be incredibly beneficial. However, Buford says in athletics and in life, it always comes down to a choice to strive for greatness.

Every quarterback is saying we're going to the Super Bowl this year, but how many of them believe that?" Buford said. "How many of them really, truly feel that this is my going to be my reality? You almost have to be delusional like that to achieve greatness in a sense. You have to see and believe something before other people can or will."

This mentality is something everyone can implement in their daily lives. Buford says the sky is the limit when a persons head is in the right place.

We all have the ability to be incredible," Buford said. "You know, we really limit ourselves and I don't know if this is a societal thing, or it's just not receiving the right messages early enough in life. But don't ever think for a minute that anyone cannot become what they want to be. Only person stopping you is you.

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The mental game: Inside the mind of an elite athlete - CBS19.tv KYTX

A team of researchers in China have genetically engineered a pig with human DNA and transplanted skin grafts onto monkeys in a milestone they say will pave the way for future skin and organ transplantations.

In the United States alone, more than 113,000 people are awaiting organ transplants yet just over 36,000 occur each year, according to the Health Resources and Services Administration. Xenotransplantation, the process of grafting or transplanting organs or tissues between different species, may be a solution to the shortage of organs around the world and provide treatment for patients with terminal organ failure, write the researchers in bioRxiv, a pre-print server for biology that has not been certified by peer-review for publication in a journal.

Pigs are widely used in biomedical research yet they are not phylogenetically close to humans, so rejection and incompatibility can occur. Genetically modifying donor pigs to serve as a potential organ source may provide a potentially viable solution, but the necessary combinations of genetic modifications in pigs for human xenotransplantation have not yet been determined.

To test these parameters, researchers at the First Affiliated Hospital of Nanchang University in China removed key pig genes that trigger organ rejection and added eight human genes to modified pigs in order to further reduce the chance of an organ being rejected. Skin was then transplanted from the pigs to monkeys and survived up to 25 days without the monkeys requiring immunosuppressive drugs.

Genetic modification of the pig is necessary to account for the differences between the pig and human genome, especially from the immune and molecular compatibility aspects, write the authors, adding that CRISPR/Cas9 technology has accelerated this process but determining which combinations remains an open question.

The authors note that extensive genome editing in certain pig cells is not a practical endeavor because of the telomere length, which requires complex and extensive editing and a long cell culture time that may lead to cell aging or death. There is also a low risk that porcine endogenous retrovirus (PERV), a virus integrated into the genomes of pigs, could infect human hosts. Even so, the findings have great potential for clinical value to save severe and large area burn patients and other human organ failure.

As the skin is considered the vital, unique and immunogenicity organ, our preliminary success in skin xenotransplantation using the combination of multi-gene modified pig in NHP provides the approval of the concept, paves a way to initiate the other organ preclinical trial and clinical trial, implies a success of these organs xenotransplantation, writes study author Wang Gang in a comment, adding that genetically altered pigs may have the potential to become an unlimited organ source for future clinical transplantation.

The researchers add that their findings may also have applications for human disease modeling and potentially help to one day establish disease-resistant animals.

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Pigs Genetically Engineered With Human Cells May Pave The Way For Future Skin Transplants - IFLScience

Researchers at KU Leuven have discovered that a defect in the ATP13A2 gene causes cell death by disrupting the cellular transport of polyamines. When this happens in the part of the brain that controls body movement, it can lead to Parkinsons disease.

With more than six million patients around the world, Parkinsons disease is one of the most common neurodegenerative disorders. Around twenty genetic defects have already been linked to the disease, but for several of these genes, we dont know what function they fulfill. The ATP13A2 gene used to be one of these genes, but researchers at KU Leuven have now discovered its function in the cell. The researchers explain how a defect in the gene can cause Parkinsons disease in their article ATP13A2 deficiency disrupts lysosomal polyamine export published in Nature.

We found that ATP13A2 transports polyamines and is crucial for their uptake into the cell, explains senior author Peter Vangheluwe, PhD, from the Laboratory of Cellular Transport Systems. Polyamines are essential molecules that support many cell functions and protect cells in stress conditions. But how polyamines are taken up and transported in human cells was still a mystery. Our study reveals that ATP13A2 plays a vital role in that process. Our experiments showed that polyamines enter the cell via lysosomes and that ATP13A2 transfers polyamines from the lysosome to the cell interior. This transport process is essential for lysosomes to function properly as the waste disposal system of the cell where obsolete cell material is broken down and recycled. However, mutations in the ATP13A2 gene disrupt this transport process, so that polyamines build up in lysosomes. As a result, the lysosomes swell and eventually burst, causing the cells to die. When this happens in the part of the brain that controls body movement, this process may trigger the motion problems and tremors related to Parkinsons disease.

Unraveling the role of ATP13A2 is an important step forward in Parkinsons research and sheds new light on what causes the disease, but a lot of work remains to be done.

Vangheluwe continues: We now have to investigate how deficient polyamine transport is linked to other defects in Parkinsons disease such as the accumulation of plaques in the brain and malfunctioning of the mitochondria, the energy factories of the cell. We need to examine how these mechanisms influence each other, he says. The discovery of the polyamine transport system in animals has implications beyond Parkinsons disease as well, because polyamine transporters also play a role in other age-related conditions, including cancer, cardiovascular diseases, and several neurological disorders. Now that we have unraveled the role of ATP13A2, we can start searching for molecules that influence its function. Our lab is already collaborating with the Centre for Drug Design and Discoverya tech transfer platform established by KU Leuven and the European Investment Fundand receives support from the Michael J. Fox Foundation.

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Function of Gene Implicated in Parkinson's Disease Discovered - Clinical OMICs News

31 Jan 2020

Soccer players who repeatedly bonk their noggins against the ball have losses in episodic memory. The losses are subtle and likely unnoticeable. This subclinical effect is strongest in ApoE4 carriers, according to a study published January 27 in JAMA Neurology.

Researchers led by Michael Lipton of Albert Einstein College of Medicine in New York correlated the previous years heading exposure with memory scores. They questioned amateur players about their degree of heading, and found that people who were ApoE4-positive and regularly headed the ball had the worst delayed recall. Whether these memory blips signify a brewing subclinical pathology that could develop into neurodegenerative disease over time remains unclear, but Lipton said the findings suggest players might do best to at least tone down the number of headers they make in each game.

Multiple studies have linked participation in the military or in rough-and-tumble contact sports, such as American football, ice hockey, and boxing, to neuropsychological problems and subsequent neurodegenerative disease. However, evidence has also been mounting that that milder, subconcussive blows to the headsuch as those sustained during intentional heading of the ball by soccer playersalso take a cognitive toll and might even spark neurodegeneration (Matser et al., 2001;Feb 2017 news; Nov 2019 news).

Ouch! (And remember to buy milk.)

Little is known about how or if ApoE4, the strongest genetic risk factor for AD, influences cognitive consequences of these repetitive actions, although previous studies reported that American football players or boxers who inherited the ApoE4 allele were at greater risk of cognitive impairment than noncarriers (Jordan et al., 1997; Kutner et al., 2000).

First author Liane Hunter and colleagues investigated verbal memory loss experienced by amateur soccer players in the New York City area. Previously, the researchers had reported that the number of times a player headed the ball over a year correlated with poorer scores on tasks of verbal learning and memory (Levitch et al., 2018). Now, they factored ApoE genotype into the equation. The Einstein Soccer Study enrolled 379 participants who had been playing soccer regularly for more than five years. Of those, 355 were genotyped for ApoE. They answered a detailed computerized questionnaire, called HeadCount-12m, which incorporated information about the number of games or practices per month, months of play per year, and the average number of headers per game, to estimate the total number of headers over the prior year. They also underwent cognitive testing.

Three of the genotyped volunteers reported heading the ball more than 100,000 times over the past year, and were excluded as extreme outliers. The remaining 352 players averaged 23 years of age; 256 were men. Eighty-one carried at least one copy of ApoE4. The players headed the ball an average of more than 600 times, ranging from 70 to 3,800 headers over the year. The researchers split the volunteers into quartiles, with the lowest two considered low heading exposure, the third moderate, the fourth high. Players in the moderate and high exposure quartiles had lower scores on the CogState International Shopping List Delayed Recall (ISRL) test, a measure of verbal memory in which participants attempt to recall a 12-item shopping list 20 minutes after having it read to them. While players with low exposure recalled an average of 10 items, those in the moderate and high exposure groups recalled 9.3 and 9.2, respectively. The ISRL serves as an outcome measure in some Alzheimers clinical trials.

ApoE4 strengthened the association between heading and poor performance on the ISRL. Among carriers, the difference in ISRL scores between high- and low-frequency heading quartiles was fourfold greater than in noncarriers. When comparing scores in people with high versus moderate exposure, ApoE4 carriers had an 8.5-fold greater deficit than did noncarriers. ApoE4 seemed to amplify the differences between groups. Translated into absolute terms, noncarriers in the highest heading quartile scored 0.36 points lower on the ISRL than noncarriers with lowest heading exposure. For ApoE4 carriers, the most eager headers scored 1.49 points lower than those in the lowest quartile. Essentially, more frequent heading caused ApoE4 carriers to forget one more item on the shopping list than did noncarriers.

Lipton told Alzforum that this dip in memory is unlikely to be noticed in daily life. The mechanism behind it is unknown. The authors speculated that, as a carrier of lipids in the brain, ApoE could play a role in repairing damaged synapses following injury, and ApoE4 may do a subpar job. Lipton previously reported that high levels of soccer heading associated with microstructural damage to myelin, and considers it possible that ApoE could play a role in myelin repair (Lipton et al., 2013).

Henrik Zetterberg of the University of Gothenburg in Sweden noted that the effect on memory attributable to ApoE4 is small, and it is unclear how the allele would contribute to memory loss in response to injury at such a young age. He speculated that differences in the way microglia or astrocytes respond to injury in ApoE4 carriers could explain subtle changes in memory. He added that serum markers of axonal injury and neuroinflammationneurofilament light (NfL) and glial fibrillary acidic protein (GFAP)could connect pieces of the puzzle in future studies. Zetterberg previously reported elevated NfL in response to soccer heading (Wallace et al., 2018).

Zetterberg thinks the verbal memory dip by itself is unlikely to portend AD or other neurodegenerative diseases. To Lipton, that is the big question left open by the study. While forgetting the milk on the shopping list may not pose an issue now, could it signify a brewing subclinical pathology that could hasten neurodegeneration?

In an accompanying editorial, Sarah Banks of the University of California, San Diego, and Jesse Mez of Boston University School of Medicine emphasize that the data from this paper cannot answer this question: It should be stated explicitly that the intellectual jump from the current study findings to late-life cognitive decline and neurodegeneration, including chronic traumatic encephalopathy, is substantial.

These authors cautioned that the findings should not be used to enact policy changessuch as using ApoE screening to inform decisions about soccer play. Lipton thinks that, conceptually, using genetics to inform decisions about risk is no longer a stretch. Even without ApoE4 in the picture, reducing heading exposure among players who do it most frequently would be feasible, Lipton noted, given that the players with high heading exposure are a minority of players. Among this NYC cohort of amateurs, roughly a third of the players fell into the highest quartile of heading.Jessica Shugart

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Soccer Heading Has Greater Impact on Memory in ApoE4 Carriers - Alzforum

You wouldnt know that Lynda Marino has a serious heart condition, save for the scar that ends near the top of her breastbone.

Marino, 40, a busy mother of two young children, is tall, slender and outgoing and fortunate to be alive.

She was diagnosed in her mid-20s with cardiomyopathy, nearly died from cardiac arrest four years ago and weathered open-heart surgery on New Years Eve at the Cleveland Clinic.

Her sister, 35-year-old Marianne Potratz, has the condition that thickens and endangers heart muscle, too.

We don't look like the average people you might expect to have heart disease, Marino said.

The two sisters have become leading advocates for the Buffalo Niagara affiliate of the American Heart Association during the last few years, not so much because their condition is rare but because heart disease is so common.

They dont want themselves or you to become another statistic for the No. 1 killer in the nation.

Cardiovascular disease can take a life suddenly or over time, at any age. Those stricken young often have a genetic predisposition like Marino, who lives in East Amherst, or Potratz, of Grand Island, but the Heart Association estimates that 80 % of cases can be prevented with healthy living and decision-making.

You need to eat right, exercise regularly and talk with your primary care provider about your family history of heart disease. Health care visits and screenings are important as often as your provider recommends, said Dr. Vijay Iyer, chief of cardiovascular medicine in the University at BuffaloJacobs School of Medicine and Biomedical Sciences.

Nobody should get to the age of 25 without knowing their blood pressure and their cholesterol numbers, he said.

Action saves lives when it comes to heart disease

Ignorance is hardly bliss when it comes to heart disease, either.

High blood pressure and even diabetes, for example, often don't manifest themselves till theyve gone too far, said Iyer, who also directs structural heart interventions at Gates Vascular Institute and the complex valve clinic at Buffalo General Medical Center.

Most of the early symptoms can be very subtle or there may be no symptoms at all, he said. People could have had hypertension for a long time, and slowly built blockages in the arteries, and the first time they show up is in the hospital when theyve had a heart attack or had a stroke so not knowing about your physical condition, your medical history, can be quite deleterious. It can be potentially fatal.

Lynda Marino, left, and her sister, Marianne Potratz, right, walk with their mother, Susan Minbiole, near the house where they grew up in East Amherst. Genetic testing after Marino suffered a cardiac arrest in 2015 showed that the sisters and their father, Barry Minbiole, have a genetic mutation that predisposes them to cardiomyopathy, a heart condition that must be closely monitored. (Robert Kirkham/Buffalo News)

It can be easy to take health for granted, particularly when you lead a busy life.

Marino knows. She learned she had cardiomyopathy in 2006, while in her mid-20s, when she was diagnosed with pneumonia. Her primary physician ordered a chest X-ray that showed signs of the condition, which thickens the heart walls, hampers blood flow and sometimes damages valves.

Marino was encouraged to see her doctor regularly, limit her exercise to moderate levels and eat right. She also was urged to be mindful of dizziness or extreme fatigue two signs of disease progression.

In the years that followed, she felt fine. She and her husband, John, chief technical officer in the Cleveland Hill School District, started a family. She also landed a job as marketing director with Canterbury Woods retirement communities.

Things changed unexpectedly on Sept. 12, 2015, when Marino went into cardiac arrest while driving home from T.J. Maxx and Aldi in the Town of Lockport.

I had a newborn son at home, she said. I had a 2-year-old daughter. I worked full time. Who knows what I was feeling, or just ignoring, beforehand because life was so insane.

Her right foot slipped off the gas as she slumped past the steering wheel onto the console. The car crawled south on Transit Road at 5 mph, while her daughter, Claire, cried frantically in a car seat behind her.

Thats when the miracles started happening, she said, recounting what others since have told her.

Chris James, a fellow motorist, saw what was happening, stopped his car, ran to the side of Marinos Forester SUV and was able to open the door because it didnt have automatic locks. He directed the car to the side of the road, turned off the ignition and called 911.

Bill and Peggy Killewald watched the commotion across four lanes of traffic while Bill, a retired veterinarian, pumped gas at a NOCO station. The couple ran to Marino, whose electrical impulses to her heart had stopped.

When Bill was doing CPR, he said I had no pulse, she said. My lips were blue and he, as a doctor, thought I was gone.

A Niagara County sheriffs deputy armed with an automated external defibrillator next joined the life-saving effort. At the time, the department was one of few in regional law enforcement that equipped its patrol cars with AEDs. Had she driven a few miles south into her home county, her odds of survival would have been worse.

Rescue workers rushed her first to Lockport Memorial Hospital, then Buffalo General, where she spent four days in an induced coma to help her recuperate.

In the coming weeks, both she, her sister and parents were tested for a gene mutation that predisposes people to cardiomyopathy.

Both sisters already knew they had the condition, confirmed through echocardiograms years earlier. They now learned they had the mutation, along with their father, Barry, 68, a retired Praxair engineer.

Nobody should get to the age of 25 without knowing their blood pressure and their cholesterol numbers, says said Dr. Vijay Iyer, a cardiologist at Gates Vascular Institute and Buffalo General Medical Center, as well as chief of cardiovascular medicine in the University at Buffalo Jacobs School of Medicine and Biomedical Sciences. (John Hickey/News file photo)

Several weeks later, surgeons at Buffalo General implanted defibrillators and pacemakers into Marino and Potratz, who have since called themselves the Sling Sisters because they needed to wear left arm supports for six weeks as they recovered.

The regional American Heart Association affiliate offered them support along the way, which is why they now share their stories as part of the Go Red for Women campaign, which encourages women to know their cardiovascular risks and take action to reduce them.

They were discouraged from eating too much salt, fatty meat and processed foods, running marathons or lifting heavy weights. They were encouraged to walk for exercise, eat more fruits, vegetables and seafood, and drink plenty of water.

Heart Association staff also encouraged the sisters to know their health screening numbers, particularly blood pressure, cholesterol, blood sugar, weight, and any sudden increases in fluid retention.

Both women also were put on beta blocker drugs to help regulate their heart rhythms.

We live very normal lives, Marino said, or at least I did for a couple of years.

She and her sister returned from a trip to Iceland and Paris in late 2018 and Marino began to experience more dizziness, shortness of breath and chest pressure when exerting herself. She led a nearly yearlong effort to find the best solution to removing substantial muscle scarring on her heart, and secure health insurance approval.

On New Years Eve, a cardiomyopathy team at the Cleveland Clinic performed an extensive myomectomy, slicing nearly a half ounce of damaged muscle from Marinos heart nearly twice as much as generally creates urgency for such open-heartsurgery.

Before this procedure was perfected, the only alternative was a heart transplant, said the sisters' mother, Susan Minbiole.

From left, Lynda Marino, Susan Minbiole and Marianne Potratz have become key supporters of the Go Red for Women campaign, which encourages women to know their cardiovascular risks and take action to reduce them. (Robert Kirkham/Buffalo News)

Marino hasnt been able to drive or lift anything heavier than a milk carton since her surgery. She has returned to the Cleveland Clinic twice since surgery and will do so less often going forward. She also continues to work with cardiologists and electrophysiologists in Buffalo.

The Minbiole family always has been tight. Marino lives just a few blocks from her parents, while Potratz and her husband, Seth, also are regulars at family gatherings that have taken on greater meaning in recent years. Family members vacation together more regularly, and their gratitude and giving has taken on greater proportions.

Friends and family members became part of the Sling Sisters team that has become a force in regional Heart Association fundraisers.

The experience also helped underline the importance of family, community and preparedness when it comes to good health.

We really promote hands-only CPR because my life was saved in part by bystanders, complete strangers, that jumped in to help me, Marino said. You could be someone else's hero by learning CPR or suggesting your friend go see the doctor because you're hearing her complain about an ache in her arm or other symptoms of heart disease.

The sisters are CPR-trained and, because there is little research on cardiomyopathy, Marino has enrolled in a Yale University study on exercise for those with the condition.

Meanwhile, they and their families marvel at medical advances that help Marino and Potratz stay on top of their challenges.

Marino has a device similar to an Apple Watch that can take an EKG, and both sisters have another device, half the size of a toaster, that takes heart readings from their pacemakers and defibrillators and transmit them by cell signal to health specialists in the event of an unusual reading.

The pacemaker and defibrillator will always be there to protect against any future cardiac arrest, Marino said. It doesn't stop it from happening, but it would stop it from killing me.

They hope more advances will come in the future and work toward that end in part because Marinos now 6-year-old daughter and 4-year-old son, Logan, also have the MYBPC3 gene mutation that predisposes them to the same condition.

As is the case for everyone, the sisters said, its better to know something like that than not.

Some say ignorance is bliss, Potratz said, but in my case, knowing that I'm protected is far more valuable than not having the information at all.

WNY's unhealthy habits could stunt economic growth, study says

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Two sisters, one near-death experience, and a warning about heart disease - Buffalo News

Genetically altering symbiotic gut bacteria in honey bees is successful at killing varroa mites, which tend to make bees sick and leave them at an increased risk of colony collapse disorder, according to a study published today (January 31) in Science.

Colony collapse disorder (CCD) occurs when the majority of a hive abandons ship, leaving behind the queen, honey and pollen stores, and young, immature bees behind. Without the workforce of a full hive, the colony fails. According to the US Department of Agriculture, there does not appear to be a single cause of CCD, rather, it is likely a combination of disease, parasites, poor nutrition, pesticide exposure, and other stressors on the hive.

One possible contributor to unhealthy hives are Varroa destructor mites, an invasive species that arrived in North America in the early 1980s. Not only do these parasites feed on the bees fat stores, but they also transmit a virus that leads to the deformation of their wings. As a bees health declines, it becomes more susceptible to contracting other illnesses. If a hive becomes infested with these mites, it might be enough of a threat for the healthy bees to bug out, leaving their hivemates behind.

To fight back against Varroa, researchers looked to Snodgrassella alvi, a symbiotic bacterium found within the gut of honey bees. Genetic modification of the microbes enabled them to destroy the mites from the inside out through RNA interference (RNAi). The engineered bacteria produced double-stranded RNA that induced the mites to launch an RNAi defense to destroy those sequences. Because the bacterial sequences matched those from the varroa genome critical to the mites survival, the silencing mechanism wiped out the mite transcripts as well, killing the parasites

It is a bit like a customized medicine for honey bees, Jeffrey Scott, an insect toxicologist at Cornell University who was not involved with the study, tells Science. Being able to engineer a gut microbe and specifically regulate gene expression in the host has enormous implications.

By using S. alvi as a manufacturer, the team was able to provide a continued supply of the RNA, providing a useful window for the bees to fight back against the mites. The effects lasted for the duration of the 15-day-long experiment and bees with the altered bacteria were 70 percent more likely to kill mites within 10 days than those without it.

If the technique works in the field, that could be the end of Varroa and the viruses, Robert Paxton, a bee ecologist at Martin Luther University who was not involved with the study, tells Science.

While the results of this small-scale experiment are encouraging, the method wont be used in the wild anytime soon. Releasing bacteria with gene-silencing potential invariably raises containment questions along with concerns that mutations may cause unintended consequences.

Youre turning off genes [via RNAi], honeybee epidemiologist Dennis vanEngelsdorp of the University of Maryland who was not involved with the study tells Science News. There has to be a very healthy debate about how do we regulate this?

Lisa Winter is the social media editor forThe Scientist. Email her at lwinter@the-scientist.com or connect on Twitter @Lisa831.

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Engineered Microbe in Bees Guts Fends off Deadly Varroa Mite - The Scientist

Asthma is the most common chronic respiratory disease in children, affecting approximately 6.1 million US children younger than 18 years.1 Asthmas hallmark characteristics chronic inflammation of the airways, bronchial hyperreactivity, airflow obstruction, and excessive mucus production lead to troublesome episodes of cough, wheezing, and dyspnea2 that require ongoing management and pose a consistent burden on the healthcare system.3

Furthermore, asthma can have a negative effect on the dailyroutines of both children and caregivers and hamper a childs academicperformance and ability to attend school. In 2013, the CDC found that 49% ofchildren with asthma reported 1 asthma-related missed school days.4

Although asthma can develop at any time throughout life, itmost often begins in childhood.5 A range of childhood risk factorsfor asthma have been identified in studies to date, including geneticsusceptibility, atopy, and microbial and environmental exposures.3

In this interview with Asthma Advisor, translationalresearcher Mitchell H. Grayson, MD, FAAAAI,FACAAI, chief of the Division of Allergy and Immunology at NationwideChildrens Hospital and professor of pediatrics at The Ohio State UniversityCollege of Medicine in Columbus, discussed the latest insights about theconnection between common viral infections and asthma in children.

AsthmaAdvisor: Which viral strains have been associated with the development of wheezingepisodes in children?

Mitchell H. Grayson, MD, FAAAAI, FACAAI: There are viruses that have been associated with the development of asthma and postviral wheeze, and then there are viruses associated with asthma exacerbations. Respiratory syncytial virus (RSV), rhinovirus, coronaviruses, and influenza have been associated with postviral wheeze and asthma onset; rhinovirus and coronaviruses have been more associated with exacerbations of existing disease than with induction of asthma.2 Also, parainfluenza virus types 1 and 3 have been associated with induction of disease, as well as exacerbation of existing asthma.2

AsthmaAdvisor: How is the number of wheezingepisodes in early childhood related to the development of asthma?

Dr Grayson: This is a complicated situation that leads to 2questions 1) What is asthma? and 2) What is a postviral wheeze? Obviously, wedo not get all excited about a child having asthma if they wheeze once, but thegray zone is when they wheeze 2 or more times.

First, there is no magic answer,but in the absence of emergency department visits or hospitalizations, if apatient wheezes more than 2 or 3 times due to viral illnesses, that patientprobably has asthma, but there is no hard and fast rule about that.

Asthma Advisor: In cases of true asthma, will asthma episodes also be provoked by other types of environmental stimuli?

Dr Grayson: Possibly; in children at least, almost all asthmais allergic asthma. Part of the problem in clearly defining asthma is thatwheezing is actually the lung being twitchy and bronchoconstrictingto an irritant of some sort it may be diesel smoke, a cat allergen, orrhinovirus, and that is where it becomes sort of problematic is this all thesame disease? We lump them together because the clinical symptoms are the same,but I would argue that the mechanisms of wheeze due to cat allergen andrhinovirus are very similar (immunoglobulin E [IgE] responses) but that dieselexhaust may not be driving asthma through an IgE response. So, there may bedifferent mechanisms upfront with the same downstream effect on the lung.

AsthmaAdvisor: How much is known about the connection between allergic sensitization andasthma? What comes first?

Dr. Grayson: Most studies have looked at sensitization at 1 year of age, and the problem is that the children were already wheezing before that. The COAST study (ClinicalTrials.gov Identifier: NCT00204841) investigators, for example, attempted mathematical modeling and proposed that rhinovirus infections cause asthma in children who already have atopic sensitization.6

There have also been some recentpublications suggesting that RSV infection leads to wheezing in children whoare not atopic to begin with vs the rhinovirus that leads to wheezing in childrenwho are atopic.2 So, there is a little confusion as to how thatmechanism is working. Generally, with RSV, the risk is in the age group between2 and 6 months2 who have a severe RSV infection; that is usually alittle young to be producing a lot of IgE vs the risk of asthma from rhinovirustends to be in children a little older, which would then align with the ideathat patients become atopic first.

There is also the atopic march, in which children develop atopic dermatitis in infancy and then allergic rhinitis by the time they are 3 or 4 years old and, finally, asthma by the time they are 5 or 6 years old. The traditional path to atopic asthma is one that develops with the atopic march, and therefore, clearly, the children are sensitized well before they start wheezing.7

AsthmaAdvisor: What are the risk factors for allergic asthma vs nonallergic asthma?

Dr Grayson: Allergies and allergic disease in the family andin the individual put one at risk for allergic asthma. Nonallergic asthma tendsto occur later in life and be more severe and is usually not associated witheosinophils in the peripheral blood and sputum.8,9 I would putviruses in the allergic asthma pot, although there have been studies thatsuggested that RSV drives nonallergic asthma. The risk factors for nonallergicasthma are not well defined and, in many ways, nonallergic asthma is theabsence of allergic asthma.

Asthma Advisor: What is the long-term outlook for children who develop allergic asthma in early childhood?

Dr Grayson: We do have children who outgrow their asthma. Inmany cases, it is like a lot of other allergic diseases that, when you get toyour 20s, seem to go away only to return in your 30s. In the vast majority of children,asthma gets better and becomes less problematic as the child gets older.10We assume that the more severe asthma is, the less likely it is that the childwill outgrow it, but we really do not have good predictors of who will outgrowtheir asthma.

AsthmaAdvisor: Is there a geneticsusceptibility in children who develop asthma after a viral infection?

Dr Grayson: I am not aware of any good studies findinga specific genetic link. There is no good genetic marker to predict if someonewill wheeze or not wheeze with a viral infection. With a family history ofatopy, you are more likely to have asthma, but whether you would have it with avirus is a different issue.

AsthmaAdvisor: How much is known about themechanism by which viral infections cause asthma exacerbations?

Dr Grayson: There are a couple of ideas about this. There was a clinical trial (ICATA Asthma Mechanistic Study; ClinicalTrials.gov Identifier: NCT00377390) where the investigators used anti-IgE therapy in children with allergic asthma and reduced asthma exacerbations in the pollen season, but they also reduced asthma exacerbations basically back to the level seen in the control group during the viral respiratory season in the winter.11 My argument would be that the anti-IgE therapy removes antiviral IgE, preventing mast cell activation and subsequent histamine release, all ending up preventing bronchoconstriction from the viral infection. If you do not have bronchoconstriction, it is likely that you will not have asthma. That is a rationale for using anti-IgE therapy to prevent viral induced wheezing and asthma.

Another explanation, proposed by the Inner-City Asthma Consortium, is that there is a certain type of dendritic cell that makes type I interferon, which is a major player in the antiviral immune response.12 Crosslinking IgE on these cells reduces the amount of type I interferon that they produce. So, if you are allergic and produce more IgE, you have an impaired immune response because you are making less type I interferon and, therefore, that leads to worsening disease.

I have 2 problems with this: First,I do not know about the mechanistic connection between type I interferon andwheeze, and second, solid data supporting the idea that viral titers are higher,or that type I interferon is markedly suppressed in patients with asthma, arelacking. We do not have a good studyusing antiviral IgE therapy at the time of initial viral infection to see if itwill prevent the development of postviral wheeze or a study where we giveindividuals a virus, whether they are or are not receiving antiviral IgEtherapy, to see if it will prevent them from wheezing.

Disclosure:Dr Grayson reported serving onadvisory boards for AstraZeneca, Genentech,Novartis, Genzyme, DBVTechnologies, and Aimmune.

References

Link:
Understanding the Links Between Asthma and Viral Infections in Children - Pulmonology Advisor